OLIVIA W. ROSSANESE Ph.D.

Research Assistant Professor of Biochemistry

Office: 802-C RRB

Phone: 615-936-8708

Email: olivia.rossanese@vanderbilt.edu

Cell/Cancer Biology

Olivia W. Rossanese, Ph.D. is a Research Assistant Professor of Biochemistry and a Cancer Cell Biology Group Leader for the Fesik Lab. Her group develops and conducts biochemical and cell-based assays to drive SAR and support cancer drug discovery. Cell Biology group is also developing and running plate-based assays to measure cell proliferation and viability, anchorage-independent growth, kinase activity, migration, apoptosis, and signaling, using a number of readouts and detection systems. Recent examples of successful assays include the RPA70-ATRIP fluorescence polarization anisotropy assay that is read on the Perkin Elmer Envision, a kinetic assay to measure Sos-catalyzed nucleotide exchange on K-Ras that is read on the Hamamatsu FDSS, and a kinase phosphorylation assay that is an adaptation of the LANCE technology. The Cell Biology group uses data from these assays in multiple cell lines to develop testable hypotheses regarding predictors of resistance and response to the targeted agents tested.

Olivia gained her pre-clinical drug discovery experience in the Oncology group at GlaxoSmithKline. She contributed to the due diligence decision regarding the in-licensing of the MEK inhibitor tramitinib (GSK2021212; currently in Phase III clinical trials), examining the effects of the inhibitor on downstream signaling. In her work on the B-Raf inhibitor program, she developed assays to directly measure phosphorylation of downstream substrates and to examine the broader consequences of target inhibition on signaling cascades. These assays were used to discover and develop inhibitors with potencies ranging from 0.1 – 10 nM against the target kinase. In addition, Oivia performed PD and efficacy studies of advanced compounds to demonstrate target and tumor growth inhibition in mouse xenograft models. She analyzed PK data from these studies to understand the relationship between dose, exposure, and response in this system. The candidate molecule from this program, debrafinib (GSK2118436), is currently in Phase III clinical trials. Olivia led and participated in efforts to discover inhibitors for additional kinases and other protein classes. For these programs, her teams and she developed cell-based assays to understand the specific molecular consequences of target inhibition, but also functional assays to understand how target inhibition contributes to the larger implications of oncogenesis. She was also focused on building and testing pre-clinical hypotheses to identify genetic markers of drug sensitivity and patient selection for specific targeted therapies.